Spirituality is an important resource used to maintain psychological well-being, physical health, and health-related quality of life (HRQOL) among women with HIV/AIDS. Few studies have examined the relationships among spirituality, health, and HRQOL in women with HIV. The purpose of this study is to investigate the relationships between spiritual well-being (SWB), depression, immune status, and HRQOL and to examine the contribution of spirituality to HRQOL beyond what is explained by psychological and physiological factors among women with HIV. A secondary data analysis will be conducted on data from 2 NIH-funded behavioral trials conducted at an Infectious Disease clinic. A sample of approximately 125 HIV+ women will be included in the analysis of SWB, depression, CD4 cell count, and HRQOL scores. Hypotheses will be tested using Pearson correlation statistics and hierarchical regression analysis. Focus group sessions and individual interviews about HIV-positive women's spiritual experience will also be conducted with 12-16 women. Interview data will be content-analyzed for emerging themes. The results of this study may facilitate future research on holistic interventions to promote the health and HRQOL of women with HIV.